October 11, 2022 12:50 PM EDT

So far, COVID-19 has come with one small silver lining for health: cases of influenza have dropped dramatically. During the first flu season during the pandemic, lockdowns kept people indoors and away from one another, limiting the virus’ ability to spread. And once people began mingling more during the next flu seasons, widespread use of masks blocked influenza’s chances of infecting large numbers of people.

But that could change this flu season, as mask mandates have disappeared and more people are interacting in close quarters in school, workplaces, sports events, public transport, and more. Health experts are warning that flu cases could rise again this winter, and that the combination of influenza and COVID-19 together could pose a real public-health threat that sends more people to the hospital and in need of intensive care. Already, the flu season in the southern hemisphere—which runs from April to October and serves as a harbinger of what’s to come for the U.S.—has been severe, with cases in Australia three times higher than average compared to the past five years. That could mean influenza will sweep through North America and Europe with equally aggressive force this winter, alongside rising cases of COVID-19.

That opens the possibility that people could get the two infections at the same time—which experts believe could be both unpleasant and dangerous. “Are two viruses that cause huge inflammatory responses together going to make that response worse? Theoretically, yes,” says Dr. Khalilah Gates, a pulmonary critical care physician at Northwestern University.

Gates and others stress that there aren’t extensive data yet to be sure exactly what will happen when people are infected with both influenza and SARS-CoV-2. But the limited early data—some from people, but mostly from animals—are not encouraging. Already, doctors know that people who get both the flu and a cold at the same time tend to be sicker than those who are only infected with one virus. The same could be true when flu and COVID-19 combine; classic symptoms, including fever, chills, fatigue, and coughing, could become more intense for some people. In one 2021 study on COVID-19 co-infections, including 17 people who tested positive for both influenza and COVID-19 at King Fahad Hospital in Medina, Saudi Arabia, their rates of hospitalization and death were higher than those for people infected with COVID-19 a type of bacteria that can cause respiratory tract infections.

In the largest study so far looking at co-infection of the two viruses, published in April, researchers at the University of Edinburgh reported similar trends. Dr. J. Kenneth Baillie, professor of experimental medicine at the university, and his colleagues analyzed the health records of more than 212,000 people admitted to hospitals in the U.K. for COVID-19, who were also tested for other infections. People infected with influenza and SARS-CoV-2 were four times as likely to need mechanical ventilation, and twice as likely to die, compared to people who just had COVID-19.

Read More: Scientists Are Worried About New COVID-19 Variants—But Most Americans Aren’t

“We can, with some confidence, say that being infected with flu and SARS-CoV-2 at the same time increases the risk of both needing to go on a ventilator and needing intensive care, and of death,” says Baillie.

Animal studies also show that those who are co-infected with SARS-CoV-2 and influenza tend to do worse than those infected with either virus alone. In March, researchers in South Korea found that co-infected mice were sicker for a longer time than those with just one viral infection, and they also had higher levels of inflammation that contributed to pneumonia. The co-infected animals also showed lower levels of virus-fighting antibodies and immune T cells against each virus, compared to mice infected with either influenza or SARS-CoV-2 alone.

In another study involving mice, published in 2020, researchers from Wuhan University reported even more concerning data on how influenza and SARS-CoV-2 might interact. They found that influenza can make it easier for SARS-CoV-2 to infect cells in the respiratory tract, including the lungs, of mice. This priming was unique to influenza, because it activates the same receptor, also found in people, that SARS-CoV-2 uses to enter and infect cells. Getting sick with the flu can therefore potentially make animals more vulnerable to getting infected with SARS-CoV-2.

“You definitely don’t want either infection, and you don’t want them together,” says Dr. Adam Ratner, director of pediatric infectious diseases at Hassenfeld Children’s Hospital at NYU Langone Health. “Together, they have the potential to be really serious and really deadly, including in people who are not elderly and without underlying health conditions.”

Another issue that concerns doctors is the fact that both influenza and COVID-19 can put people at higher risk of other infections, most notably pneumonia. Getting infected with both either at the same time, or in quick succession, could make people more vulnerable to additional infections as well.

While treatments exist for both influenza and COVID-19, there aren’t strong data assuring doctors and patients that combining them will be safe or effective. The antiviral drugs Tamiflu for influenza and Paxlovid (nirmatrelvir-ritonavir) or Lagevrio (molnupiravir) for SARS-CoV-2 can minimize the severity of symptoms of either disease, but must be taken soon after infection begins. That could be challenging for patients and doctors to determine, and missing the optimal treatment window may prevent the medications from controlling the virus well.

Read More: To Avoid Paxlovid Rebound, Some Experts Call for Longer Courses of Treatment

Baillie says that while his study showed that the risks of needing intensive care or dying are higher if people are infected with both influenza and SARS-CoV-2, it’s not clear if the people who are getting hospitalized are already at higher risk of more severe outcomes. Because both flu and COVID-19 can cause mild symptoms in some people, it may be the case that there is more co-infection occurring in the population that isn’t severe and doesn’t require medical care. Studies so far have estimated that anywhere from about 1% to 4.5% of people might be infected with both viruses—although this may be an underestimate, since most of those studies included people who were tested at hospitals and therefore might have been sick enough to need additional care.

Still, the potential that the two viruses could put some people at higher risk of needing ventilators or additional health care is making doctors wary. “As an intensive-care doctor, I’m bracing myself for a difficult winter,” says Baillie. “Whatever happens, hospitals are already busy worldwide with COVID-19 still circulating, and are fully expecting with flu that more patients will require intensive care, so I think it will be a difficult winter for hospitals and ICUs.”

Fortunately, there are things people can do to protect themselves from the likelihood of getting infected with either virus. Getting vaccinated against both the flu and COVID-19, including getting the latest COVID-19 booster shot—which targets the variant that’s causing most infections now—can lower both the chances of getting infected and of developing severe disease. Wearing masks, especially in crowded indoor settings where there is poor ventilation, could also help. “I don’t want flu and COVID-19 together,” says Gates. “I don’t want to know what that feels like, so I’m going to keep my mask on if I’m inside or around people that I’m not familiar with their vaccine status.”

Gates says she is closely monitoring cases in her community for her daughter as well. Because she didn’t want her to feel different from other students, most of whom aren’t wearing masks in class, she and her husband decided to allow her daughter to go to school without a mask. But if cases of either flu or COVID-19 increase at the school or in their community, she will ask her daughter to start wearing a mask.

Taking steps like these will be important for not only lowering individual people’s risk of getting infected with either or both viruses, but for keeping rates of disease down in the country overall.

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